Serological autoimmune profile of systemic lupus erythematosus in deep and non-deep endometriosis patients

Several studies have reported a high prevalence of autoimmune diseases such as systemic lupus erythematosus (SLE) in endometriosis patients. The aim of this study was to evaluate the SLE autoimmune antibody profile in patients with deep (DE) and non-deep endometriosis (Non-DE).Four groups of premenopausal patients were evaluated: patients with DE (n = 50); patients with ovarian endometriomas (Non-DE; n = 50); healthy patients without endometriosis (C group; n = 45); and SLE patients without endometriosis (SLE group; N = 46). Blood samples were obtained and the standard SLE autoimmune profile was evaluated in all patients. Pain symptoms related to endometriosis and clinical SLE manifestations were also recorded.The DE group presented a statistically significant higher proportion of patients with antinuclear antibodies (ANA) (20%) compared to the Non-DE group (4%) and C group (2.2%). Levels of complement were more frequently lower among DE and Non-DE patients although differences did not reach statistical significance. Similarly, anti-dsDNA antibodies and anticoagulant lupus were positive in more patients of the DE group but did not reach statistical significance. The DE group complained of more arthralgia and asthenia compared to the Non-DE and C groups.The results of this study showed higher positivity of ANA and greater arthralgia and asthenia in patients with DE compared with Non-DE patients and healthy controls, suggesting that they may have a higher susceptibility to autoimmune diseases and present more generalized pain.Copyright © 2023. Published by Elsevier B.V

Risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated to chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study performed in eight fetal-medicine units in Spain, Belgium and Bulgaria. Two populations were included: first, all singleton pregnancies attending to their first-trimester assessment in Murcia, Spain, and second, all singleton pregnancies having a CVS following first-trimester assessment at any of the participating centers. We used propensity score matching analysis to estimate the association between CVS and miscarriage. We compared risks of miscarriage of CVS and non-CVS groups after propensity score matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that lead to CVS, in a similar way in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22,250 participants in the non-CVS group and 3,613 in the CVS group. The incidence of miscarriage in the CVS group was 2.1% (77/3,613), which was significantly higher than the 0.9% (207/22,250) in the non-CVS group (p <0.001). The propensity score algorithm matched 2,122 CVS cases with 2,122 non-CVS cases including 40 (1.9%) and 55 (2.6%) miscarriages in the CVS and non-CVS groups, respectively (OR 0.72 [95% CI 0.48 to 1.10]; p = 0.146). However, we found a significant interaction between the CVS risk of miscarriage and the risk of aneuploidies, suggesting a different effect of the CVS for different baseline characteristics in such a way that, when the risk of aneuploidies is low, the risk after CVS increases (OR 2.87 [95% CI 1.13 to 7.30]) but when the risk is high, the risk after CVS is paradoxically reduced (OR 0.47 [95% CI 0.28 to 0.76]), presumably due to prenatal diagnosis and termination of major aneuploidies that would have otherwise resulted in spontaneous miscarriage. CONCLUSIONS: The risk of miscarriage in women having a CVS is about 1% higher than in women without CVS, although this excess risk is not entirely due to the invasive procedure but to some extent the demographic and pregnancy characteristics of the patient undergoing CVS. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage about three times above the patient's background-risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors, the risk of miscarriage after CVS will still remain low and similar to or slightly higher than that of the general population. For example, if her risk of aneuploidy is 1 in a 1,000 (0.1%), her risk of miscarriage after CVS will increase to 0.3% (0.2% higher)

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved

Inactivation of respiratory syncytial virus by zinc finger reactive compounds

<p>Abstract</p> <p>Background</p> <p>Infectivity of retroviruses such as HIV-1 and MuLV can be abrogated by compounds targeting zinc finger motif in viral nucleocapsid protein (NC), involved in controlling the processivity of reverse transcription and virus infectivity. Although a member of a different viral family (<it>Pneumoviridae</it>), respiratory syncytial virus (RSV) contains a zinc finger protein M2-1 also involved in control of viral polymerase processivity. Given the functional similarity between the two proteins, it was possible that zinc finger-reactive compounds inactivating retroviruses would have a similar effect against RSV by targeting RSV M2-1 protein. Moreover, inactivation of RSV through modification of an internal protein could yield a safer whole virus vaccine than that produced by RSV inactivation with formalin which modifies surface proteins.</p> <p>Results</p> <p>Three compounds were evaluated for their ability to reduce RSV infectivity: 2,2'-dithiodipyridine (AT-2), tetraethylthiuram disulfide and tetramethylthiuram disulfide. All three were capable of inactivating RSV, with AT-2 being the most potent. The mechanism of action of AT-2 was analyzed and it was found that AT-2 treatment indeed results in the modification of RSV M2-1. Altered intramolecular disulfide bond formation in M2-1 protein of AT-2-treated RSV virions might have been responsible for abrogation of RSV infectivity. AT-2-inactivated RSV was found to be moderately immunogenic in the cotton rats <it>S.hispidus </it>and did not cause a vaccine-enhancement seen in animals vaccinated with formalin-inactivated RSV. Increasing immunogenicity of AT-2-inactivated RSV by adjuvant (Ribi), however, led to vaccine-enhanced disease.</p> <p>Conclusions</p> <p>This work presents evidence that compounds that inactivate retroviruses by targeting the zinc finger motif in their nucleocapsid proteins are also effective against RSV. AT-2-inactivated RSV vaccine is not strongly immunogenic in the absence of adjuvants. In the adjuvanted form, however, vaccine induces immunopathologic response. The mere preservation of surface antigens of RSV, therefore may not be sufficient to produce a highly-efficacious inactivated virus vaccine that does not lead to an atypical disease.</p

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives inflammation. We hypothesize that in silico methods would help bridge in vitro hepatocyte data and clinical T/HS, in which the liver is a primary site of inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O 2) or normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex™ technology. Statistical analysis and data-driven modeling were employed to characterize the main components of the cellular response. Statistical analyses, hierarchical and k-means clustering, Principal Component Analysis, and Dynamic Network Analysis suggested MCP-1/CCL2 and IL-1α as central coordinators of hepatocyte-mediated inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer intensive care unit lengths of stay, and prolonged requirement for mechanical ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a main driver of the response of hepatocytes in vitro and as a biomarker for clinical outcomes in T/HS, and suggests an experimental and computational framework for discovery of novel clinical biomarkers in inflammatory diseases. © 2013 Ziraldo et al

Environmental Temperature Affects Prevalence of Blood Parasites of Birds on an Elevation Gradient: Implications for Disease in a Warming Climate

Background: The rising global temperature is predicted to expand the distribution of vector-borne diseases both in latitude and altitude. Many host communities could be affected by increased prevalence of disease, heightening the risk of extinction for many already threatened species. To understand how host communities could be affected by changing parasite distributions, we need information on the distribution of parasites in relation to variables like temperature and rainfall that are predicted to be affected by climate change.\ud \ud Methodology/Principal Findings: We determined relations between prevalence of blood parasites, temperature, and seasonal rainfall in a bird community of the Australian Wet Tropics along an elevation gradient. We used PCR screening to investigate the prevalence and lineage diversity of four genera of blood parasites (Plasmodium, Haemoproteus, Leucocytozoon and Trypanosoma) in 403 birds. The overall prevalence of the four genera of blood parasites was 32.3%, with Haemoproteus the predominant genus. A total of 48 unique lineages were detected. Independent of elevation, parasite prevalence was positively and strongly associated with annual temperature. Parasite prevalence was elevated during the dry season.\ud \ud Conclusions/Significance: Low temperatures of the higher elevations can help to reduce both the development of avian haematozoa and the abundance of parasite vectors, and hence parasite prevalence. In contrast, high temperatures of the lowland areas provide an excellent environment for the development and transmission of haematozoa. We showed that rising temperatures are likely to lead to increased prevalence of parasites in birds, and may force shifts of bird distribution to higher elevations. We found that upland tropical areas are currently a low-disease habitat and their conservation should be given high priority in management plans under climate change